Benign peripheral nerve tumours of the upper limb, predominantly schwannomas, pose unique diagnostic, therapeutic, and psychological challenges. The literature on diagnostic accuracy, surgical outcomes, patient experiences, and proteomic composition is inconclusive. This thesis aims to comprehensively evaluate the symptomatology, diagnostic precision, surgical outcomes, patient experiences, and explore the proteome heterogeneity of these tumours.

A multifaceted approach was employed across five studies, utilising retrospective clinical data, national quality registry data (HAKIR; hakir.se), prospective longitudinal patient-reported outcome measures (PROMs), qualitative semi-structured interviews, and exploratory proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry.

Preoperative magnetic resonance imaging (MRI) demonstrated high sensitivity (85%) but low specificity (50%) for identifying schwannomas, highlighting the persistence of diagnostic uncertainty prior to surgery. While preoperative tumour size did not correlate with presenting symptoms, larger schwannomas were significantly associated with persistent postoperative sensory dysfunction at last follow-up. Surgery provided robust symptomatic relief, significantly reducing overall upper limb disability, improving daily activities, and decreasing multiple pain modalities, with improvements maintained up to 12 months postoperatively.

Furthermore, long-term follow-up (median 6 years) confirmed that residual disability remains low, although mild numbness, tingling, weakness, and cold sensitivity can persist. Importantly, no significant seasonal variation (colder versus warmer seasons of the year in Sweden) was observed in postoperative symptoms, and simple linear regressions showed no significant association between documented preoperative symptoms and long-term patient-reported outcomes.

From a patient perspective, the diagnostic and treatment trajectory is frequently accompanied by profound psychological strain and anxiety, often driven by fears of malignancy and uncertainty regarding surgical risks. Patients navigated these challenges using various coping strategies and emphasised the need for clear communication and shared decision-making with healthcare providers.

At the molecular level, exploratory proteomic profiling of histologically uniform schwannomas revealed pronounced inter-tumour heterogeneity. Tumours clustered into distinct proteomic subgroups, driven by coordinated differences in proteins associated with keratinocyte differentiation, iron handling, innate immunity, and cellular metabolism, suggesting the existence of unique biological states beyond routine histopathology.

In summary, surgical excision of benign upper-limb nerve tumours is highly effective for pain relief and functional restoration, though patients should be counselled about the potential for persistent, albeit mild, sensory disturbances. To optimise care, clinicians should integrate clinical assessments with empathetic, patient-centred communication to mitigate preoperative anxiety. Finally, the discovery of underlying proteomic heterogeneity in schwannomas challenges the traditional view of these tumours as a uniform entity, paving the way for future molecular stratification that may ultimately improve diagnostic accuracy and possibly refine treatment prognosis.